Pharmacokinetic Studies of Three Alkaloids in Rats After Intragastrical Administration of Lycopodii Herba Extract by LC-MS/MS.

Dongke Ma,Xin Di,Xin Wang,Xiaoting Gu,Youping Liu

doi:10.3390/molecules24101930

Dongke Ma, Xin Di + Show 3 more

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https://doi.org/10.3390/molecules24101930

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Abstract

Lycopodii Herba is a widely used traditional medicinal herb, and contains diverse fascinating alkaloids. In this study, a fast and sensitive LC-MS/MS method for the simultaneous determination of lycodoline, α-obscurine, and N-demethyl-α-obscurine from Lycopodii Herba in rat plasma and brain tissue was developed and validated. Biological samples were extracted via a protein precipitation procedure using methanol as the extraction solvent and Huperzine B as the internal standard. Chromatographic separation was carried out using a Thermo Syncronis-C18 column (50 mm × 2.1 mm, 5 μm) and a gradient mobile phase containing methanol and water with 0.05% formic acid. The three alkaloids were detected by positive electrospray ionization in selective reaction monitoring mode. The selectivity, crosstalk, carryover effect, linearity, accuracy, precision, extraction recovery, matrix effect, and stability of the current method were validated. Then, using the validated method, the plasma pharmacokinetics and brain tissue distribution of the alkaloids in rats were investigated after intragastrical administration of Lycopodii Herba extract. The three alkaloids were shown to be rapidly absorbed into the blood (Tmax, 0.79–1.58 h), and then also eliminated rapidly (t1/2, 1.27–2.24 h). All of them could pass through the blood–brain barrier. The method provides a new research approach to expand preclinical studies of Lycopodii Herba.

Highlights

IntroductionLycopodii Herba (the dried whole plant of Lycopodium japonicum Thunb., Lycopodiaceae) is a traditional medicinal herb that is found throughout eastern Asia, especially in the southern and eastern areas of China [1]
Lycopodii Herba is a traditional medicinal herb that is found throughout eastern Asia, especially in the southern and eastern areas of China [1]
According to the chemist Ayer [19], Lycopodium alkaloids can be divided into four structural types; namelylycopodine-type, lycodine-type, fawcettimine-type, and miscellaneous-type, which typically contain lycodoline (LDL), α-obscurine (OSR), fawcettimine, and phlegmarine [13], respectively

Summary

Introduction

Lycopodii Herba (the dried whole plant of Lycopodium japonicum Thunb., Lycopodiaceae) is a traditional medicinal herb that is found throughout eastern Asia, especially in the southern and eastern areas of China [1]. It has been officially recorded in the Chinese Pharmacopoeia; possesses anti-inflammation activity [2,3], antioxidative activity [4], and antitumor activity [5]; and has been traditionally used for the prevention and treatment of various diseases such as rheumatoid arthritis, contusion, quadriplegia, dysmenorrhea, and other health problems [6,7,8]. According to the chemist Ayer [19], Lycopodium alkaloids can be divided into four structural types; namelylycopodine-type, lycodine-type, fawcettimine-type, and miscellaneous-type, which typically contain lycodoline (LDL), α-obscurine (OSR), fawcettimine, and phlegmarine [13], respectively

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